Neuroimmune Regulation of JC Virus by Intracellular and Extracellular Agnoprotein.
Neuroimmune Regulation of JC Virus by Intracellular and Extracellular Agnoprotein.
复制标题
DOI：
10.1007/s11481-017-9770-5
复制
发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Sariyer IK
中科院分区：
文献类型：
--
作者：
Craigie M;Cicalese S;Sariyer IK
JC 病毒 (JCV) 是一种人类多瘤病毒，也是脱髓鞘疾病进行性多灶性白质脑病 (PML) 的病原体。在患有潜在免疫功能低下的患者中观察到 PML，这表明外周免疫细胞和神经胶质细胞之间的神经免疫相互作用在控制大脑中的病毒再激活中发挥着重要作用。关于神经胶质细胞中 JCV 重新激活的免疫生物学以及免疫、神经胶质和病毒在这种调节中的作用，人们知之甚少。我们之前已经证明，agno蛋白（一种小的 JCV 调节蛋白）从受感染的细胞中释放出来，并被邻近的旁观者细胞内化。在这里，我们研究了细胞外和细胞内无视蛋白在 JC 病毒的神经免疫反应中的可能作用。我们的研究结果表明，暴露于不可知蛋白的神经胶质细胞分泌的GM-CSF显着减少，这是由不可知蛋白诱导的GM-CSF转录抑制介导的。同样，用无视蛋白处理的单核细胞显示出分化和成熟的改变。此外，暴露于无视蛋白的单核细胞和小胶质细胞的吞噬活性显着降低。此外，当使用体外血脑屏障模型时，无视蛋白治疗导致单核细胞响应激活的星形胶质细胞穿过内皮细胞层的迁移减少。总而言之，这些结果揭示了 CNS 内 JCV 感染期间 agno 蛋白的新型免疫调节功能，并开辟了一条新的研究途径，以更好地了解有 PML 风险的患者中与 JCV 再激活相关的机制。
JC virus (JCV) is a human polyomavirus and the etiologic agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). PML is observed in patients with underlying immunocompromising conditions, suggesting that neuro-immune interactions between peripheral immune cells and neuro-glia play an important role in controlling viral reactivation in the brain. There is little known about the immunobiology of JCV reactivation in glial cells and the role of immune, glial, and viral players in this regulation. We have previously showed that agnoprotein, a small JCV regulatory protein, is released from infected cells and internalized by neighboring bystander cells. Here we have investigated the possible role of extracellular and intracellular agnoprotein in the neuroimmune response to JC virus. Our findings suggest that glial cells exposed to agnoprotein secrete significantly less GM-CSF, which is mediated by agnoprotein induced suppression of GM-CSF transcription. Likewise, monocytes treated with agnoprotein showed altered differentiation and maturation. In addition, monocytes and microglial cells exposed to agnoprotein showed a significant reduction in their phagocytic activities. Moreover, when an in vitro blood-brain barrier model was used, agnoprotein treatment resulted in decreased monocyte migration through the endothelial cell layer in response to activated astrocytes. All together, these results have revealed a novel immunomodulatory function of agnoprotein during JCV infection within the CNS and open a new avenue of research to better understand the mechanisms associated with JCV reactivation in patients who are at risk of developing PML.
登录
查看更多内容
影响因子：
5.4
作者：
Monaco, MCG;Atwood, WJ;Major, EO
通讯作者：
Major, EO
影响因子：
11.2
作者：
Jelcic, Ivan;Jelcic, Ilijas;Martin, Roland
通讯作者：
Martin, Roland
影响因子：
12.7
作者：
Okada, Y;Sawa, H;Nagashima, K
通讯作者：
Nagashima, K
影响因子：
4.8
作者：
Craigie M;Regan P;Otalora YL;Sariyer IK
通讯作者：
Sariyer IK
影响因子：
3.2
作者：
Koralnik, IJ
通讯作者：
Koralnik, IJ